Vascular calcification in type-2 diabetes and cardiovascular disease: Integrative roles for OPG, RANKL and TRAIL

Harper, Emma; Forde, Hannah; Davenport, Colin; Rochfort, Keith D.; Smith, Diarmuid; Cummins, Philip M.

doi:10.1016/j.vph.2016.02.003

Cited by 115 publications

(96 citation statements)

References 132 publications

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“…67,68 Vascular smooth muscle cells (vSMC) can undergo osteogenic transformation into phenotypically distinct osteoblast-like cells that are capable of expressing and releasing osteochondrogenic proteins. 69 Such changes have rarely been observed in vivo in humans. Cell death can also provide phospholipid-rich debris that serve to nucleate apatite.…”

Section: Major Mechanisms Of Vascular Calcificationmentioning

confidence: 99%

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Pathology of Human Coronary and Carotid Artery Atherosclerosis and Vascular Calcification in Diabetes Mellitus

Yahagi

Kolodgie

Lutter

et al. 2017

ATVB

378

315

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The continuing increase in the prevalence of diabetes in the general population is predicted to result in a higher incidence of cardiovascular disease. Although the mechanisms of diabetes associated progression of atherosclerosis are not fully understood, at clinical and pathological level, there is an appreciation of increased disease burden and higher levels of arterial calcification in these subjects. Plaques within the coronary arteries of patients with diabetes generally exhibit larger necrotic cores and significantly greater inflammation consisting mainly of macrophages and T lymphocytes relative to patients without diabetes. Moreover, there is a higher incidence of healed plaque ruptures and positive remodeling in hearts from subjects with type 1 diabetes (T1D) and type 2 diabetes (T2D), suggesting a more active atherogenic process. Lesion calcification in the coronary, carotid and other arterial beds is also more extensive. While the role of coronary artery calcification in identifying cardiovascular disease and predicting its outcome is undeniable, our understanding of how key hormonal and physiological alterations associated with diabetes such as insulin resistance and hyperglycemia influence the process of vascular calcification continues to grow. Important drivers of atherosclerotic calcification in diabetes include oxidative stress, endothelial dysfunction, alterations in mineral metabolism, increased inflammatory cytokine production, and release of osteoprogenitor cells from the marrow into the circulation. Our review will focus on the pathophysiology of T1D- and T2D-associated vascular disease with particular focus on coronary and carotid atherosclerotic calcification.

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Section: Major Mechanisms Of Vascular Calcificationmentioning

confidence: 99%

“…78, 79 Mice deficient in a decoy receptor for RANKL, osteoprotegerin (OPG), develop extensive vascular calcification which is reduced by OPG treatment. 69 …”

Section: Hyperglycemic Mechanisms Of Diabetic Calcificationmentioning

confidence: 99%

Pathology of Human Coronary and Carotid Artery Atherosclerosis and Vascular Calcification in Diabetes Mellitus

Yahagi

Kolodgie

Lutter

et al. 2017

ATVB

378

315

View full text Add to dashboard Cite

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“…Increases in phosphate concentration in vascular smooth muscle cells induce a switch toward an osteoblast-like phenotype. Subsequently, osteogenic-primed vascular smooth muscle cells express alkaline phosphatase and secrete bone-associated proteins accompanied by the release of mineralization-competent matrix vesicles [9]. Changes in promoters or inhibitors of mineralization also affect calcification.…”

Section: Figmentioning

confidence: 99%

Calcified Nodule as the Cause of Acute Coronary Syndrome: Connecting Bench Observations to the Bedside

Sakamoto¹,

Virmani²,

Finn³

et al. 2018

Cardiology

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“…The involvement of the RANKL/RANK/OPG axis has been investigated in different autoimmune diseases that are accompanied by disturbed bone metabolism, such as different forms of arthritis, inflammatory bowel diseases, and diabetes [11][12][13][14]. It seems that the RANKL/RANK/OPG system has an even broader biological role, regulating processes such as mammary gland development during pregnancy [15], cancer cell migration [16], and cardiovascular disease [14,17,18].…”

Section: Introductionmentioning

confidence: 99%

RANKL/RANK/OPG Axis Is Deregulated in the Cerebrospinal Fluid of Multiple Sclerosis Patients at Clinical Onset

Glasnović

Stojić

Dežmalj

et al. 2018

Neuroimmunomodulation

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Objectives: Our study focused on the RANKL (receptor activator of nuclear factor-κB ligand)/RANK/OPG (osteoprotegerin) axis and selected proinflammatory/immunoregulatory upstream mediators in the peripheral blood (PBL) and cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients. Methods: PBL and CSF were collected from healthy controls (n = 35) and MS patients at the clinical onset of the disease (n = 33). In addition, PBL samples were obtained from relapse-remitting (RR)-MS patients (n = 30). Patients were assessed by means of the expanded disability status scale (EDSS) and routine laboratory parameters. Soluble (s)RANKL and OPG were measured in the CSF and plasma; gene expression was detected for RANKL, RANK, OPG, and selected cytokines/chemokines (interleukin [IL]-4, IL-10, IL-17, CCL2, and CXCL12) in PBL mononuclear cells. Results: The OPG level in the CSF was lower in MS patients at clinical onset than in controls. Moreover, the sRANKL/OPG ratio was higher in the CSF of MS patients at clinical onset and in the plasma of RR-MS patients than in controls. Gene expression of RANKL/RANK/OPG in PBL mononuclear cells was higher only in RR-MS patients. IL-4, CCL2, and CXCL12 were positively correlated and IL-10 was negatively correlated with RANKL/RANK expression. OPG was negatively correlated with EDSS and alkaline phosphatase level. Conclusion: Our study revealed that changes of RANKL/RANK/OPG axis are associated with MS, particularly the decreased OPG level in the CSF at disease onset. Therefore, these factors may serve as disease biomarkers and molecular targets of novel therapeutic approaches.

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Vascular calcification in type-2 diabetes and cardiovascular disease: Integrative roles for OPG, RANKL and TRAIL

Cited by 115 publications

References 132 publications

Pathology of Human Coronary and Carotid Artery Atherosclerosis and Vascular Calcification in Diabetes Mellitus

Pathology of Human Coronary and Carotid Artery Atherosclerosis and Vascular Calcification in Diabetes Mellitus

Calcified Nodule as the Cause of Acute Coronary Syndrome: Connecting Bench Observations to the Bedside

RANKL/RANK/OPG Axis Is Deregulated in the Cerebrospinal Fluid of Multiple Sclerosis Patients at Clinical Onset

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